Action Points

Patients with early chronic obstructive pulmonary disease showed improved lung function and quality of life (QoL) when treated with tiotropium bromide (Spiriva).

Note that tiotropium resulted in a lower frequency of acute exacerbations of COPD than placebo and improved quality of life in patients with GOLD stage 1 or 2 COPD.

Patients with early chronic obstructive pulmonary disease showed improved lung function when treated with tiotropium bromide (Spiriva), but it was unclear if early intervention altered the course of the pulmonary disease, according to Chinese researchers.

In a double-blind, placebo-controlled trial, patients with GOLD stage 1 or 2-stage COPD treated once-daily with the the inhaled, long-acting bronchodilator had reduced rate of decline in the forced expiratory volume in 1 second (FEV1) and reduced risk for exacerbations compared to placebo-treated patients, reported Yumin Zhou, MD, PhD, of the Guangzhou Institute of Respiratory Disease in Guangzhou, and colleagues.

The annual decline in the FEV1 after bronchodilator use was significantly less in the tiotropium group than in the placebo group at 29 ml per year versus 51 ml per year, for a difference of 22 ml per year (95% CI 6-37, P=0.006), they wrote in the New England Journal of Medicine.

Also, adverse event incidence was similar in the two groups, the authors noted.

Tiotropium is a long-acting muscarinic antagonist (LAMA) approved to improve airflow in patients with moderate-to-severe COPD. Small trials and subgroup analyses have shown tiotropium therapy to improve lung function, measured by FEV1 and forced vital capacity (FVC) in patients with GOLD stage 1 and early stage 2 disease.

The primary study endpoint was the between-group difference in the change from baseline to 24 months in FEV1 before bronchodilator use. Secondary endpoints included between-group difference in the change from baseline to 24 months in FEV1 after bronchodilator use, and between group difference in annual decline in FEV1 before and after bronchodilator use from day 30 to month 24.

The final analysis included 388 patients treated with tiotropium and 383 patients randomized to placebo.

FEV1 in patients treated with tiotropium was higher than in those who received placebo throughout the trial with mean differences ranging from 127 to 169 ml before bronchodilator use and 71 to 133 ml after bronchodilator use (P<0.001 for all comparisons).

The authors reported "no significant amelioration" of the mean annual decline in the FEV1 before bronchodilator use. Specifically, the decline was 38 ml per year in the tiotropium group and 53 ml per year in the placebo group for a difference of 15 ml per year (95% CI −1 to 31, P=0.06)

Post hoc analysis showed the beneficial effects of tiotropium in patients with a COPD Assessment Test (CAT) score of less than 10 and in patients with GOLD stage 1 COPD.

"This trial showed that tiotropium was effective in improving lung function and quality of life and resulted in a lower frequency of acute COPD exacerbations than placebo among patients with GOLD stage 1 or 2 disease," the researchers wrote, adding that it remains to be determined if early treatment with tiotropium alters the long-term course of COPD.

R. Stokes Peebles, MD, of Vanderbilt University Medical Center in Nashville told MedPage Today that the observed decrease in FEV1 decline in these early-stage patients was notable.

"This is important because the only other intervention in COPD that is currently known to be disease modifying is smoking cessation," he wrote. "While smoking cessation is eminently preferable, the possibility that tiotropium might alter the loss of lung function has the potential to be important."

However, Peebles cautioned that the study results from a Chinese population may not be generalizable.

Bio-fuel exposure is an important contributor to COPD in China, and more than 20% of the study cohort had never smoked cigarettes.

"It will be important to replicate this study in the U.S. to determine if the same results are seen in a different patient population with a potentially different disease pathology," Peebles noted. "It is also unclear how compliant patients will be with a daily inhaled medication, particularly an expensive one, when they have mild disease."

In an accompanying editorial, Gary Wong, MD, and Fanny W.S. Ko, MD, both of Prince of Wales Hospital, Chinese University of Hong Kong, questioned whether other LAMAs or long-acting beta-agonists (LABAs), or a combination of the two, may also slow lung function declines and improve QoL in patients with early-stage COPD.

"Early intervention and treatment for patents with diabetes mellitus and hypertension certainly lead to better outcomes," they wrote. "Is such an early treatment strategy possible and effective for patients with mild COPD?"

The editorialists called for studies of newer drugs and different combinations to answer the question.

"For now, the evidence supports the judicious use of treatment in patients with symptomatic early-stage COPD or in those who are recovering from an exacerbation," they concluded.

The study was funded by Boehringer Ingelheim and supported by the National Key Technology Research and Development Program of the 12th and the Guangdong Provincial Science and Technology Research Department.

Zhou and co-authors disclosed no relevant relationships with industry.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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